Academic literature on the topic 'ADN ligase IV'
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Journal articles on the topic "ADN ligase IV"
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Tomkinson, Alan E., Tasmin Naila, and Seema Khattri Bhandari. "Altered DNA ligase activity in human disease." Mutagenesis 35, no. 1 (October 20, 2019): 51–60. http://dx.doi.org/10.1093/mutage/gez026.
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Abstract The joining of interruptions in the phosphodiester backbone of DNA is critical to maintain genome stability. These breaks, which are generated as part of normal DNA transactions, such as DNA replication, V(D)J recombination and meiotic recombination as well as directly by DNA damage or due to DNA damage removal, are ultimately sealed by one of three human DNA ligases. DNA ligases I, III and IV each function in the nucleus whereas DNA ligase III is the sole enzyme in mitochondria. While the identification of specific protein partners and the phenotypes caused either by genetic or chemical inactivation have provided insights into the cellular functions of the DNA ligases and evidence for significant functional overlap in nuclear DNA replication and repair, different results have been obtained with mouse and human cells, indicating species-specific differences in the relative contributions of the DNA ligases. Inherited mutations in the human LIG1 and LIG4 genes that result in the generation of polypeptides with partial activity have been identified as the causative factors in rare DNA ligase deficiency syndromes that share a common clinical symptom, immunodeficiency. In the case of DNA ligase IV, the immunodeficiency is due to a defect in V(D)J recombination whereas the cause of the immunodeficiency due to DNA ligase I deficiency is not known. Overexpression of each of the DNA ligases has been observed in cancers. For DNA ligase I, this reflects increased proliferation. Elevated levels of DNA ligase III indicate an increased dependence on an alternative non-homologous end-joining pathway for the repair of DNA double-strand breaks whereas elevated level of DNA ligase IV confer radioresistance due to increased repair of DNA double-strand breaks by the major non-homologous end-joining pathway. Efforts to determine the potential of DNA ligase inhibitors as cancer therapeutics are on-going in preclinical cancer models.
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Gu, Jiafeng, Haihui Lu, Brigette Tippin, Noriko Shimazaki, Myron F. Goodman, and Michael R. Lieber. "XRCC4:DNA ligase IV can ligate incompatible DNA ends and can ligate across gaps." EMBO Journal 26, no. 14 (July 25, 2007): 3506–7. http://dx.doi.org/10.1038/sj.emboj.7601729.
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Tseng, Hui-Min, David Shum, Bhavneet Bhinder, Sindy Escobar, Nicholas J. Veomett, Alan E. Tomkinson, David Y. Gin, Hakim Djaballah, and David A. Scheinberg. "A High-Throughput Scintillation Proximity-Based Assay for Human DNA Ligase IV." ASSAY and Drug Development Technologies 10, no. 3 (June 2012): 235–49. http://dx.doi.org/10.1089/adt.2011.0404.
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Malu, Shruti, Pablo De Ioannes, Mikhail Kozlov, Marsha Greene, Dailia Francis, Mary Hanna, Jesse Pena, et al. "Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs." Journal of Experimental Medicine 209, no. 5 (April 23, 2012): 955–63. http://dx.doi.org/10.1084/jem.20111437.
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Artemis is an endonuclease that opens coding hairpin ends during V(D)J recombination and has critical roles in postirradiation cell survival. A direct role for the C-terminal region of Artemis in V(D)J recombination has not been defined, despite the presence of immunodeficiency and lymphoma development in patients with deletions in this region. Here, we report that the Artemis C-terminal region directly interacts with the DNA-binding domain of Ligase IV, a DNA Ligase which plays essential roles in DNA repair and V(D)J recombination. The Artemis–Ligase IV interaction is specific and occurs independently of the presence of DNA and DNA–protein kinase catalytic subunit (DNA-PKcs), another protein known to interact with the Artemis C-terminal region. Point mutations in Artemis that disrupt its interaction with Ligase IV or DNA-PKcs reduce V(D)J recombination, and Artemis mutations that affect interactions with Ligase IV and DNA-PKcs show additive detrimental effects on coding joint formation. Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs.
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Srivastava, Abhishek, Neetu Srivastava, Umesh NathTripathi, and Afshan Siddiqui. "Synthesis and Characterization of Mixed Ligand Complexes of Zirconium(IV) with Sulphur, Nitrogen and Oxygen Donor Ligands." Chemistry & Chemical Technology 13, no. 1 (March 5, 2019): 23–32. http://dx.doi.org/10.23939/chcht13.01.023.
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Ahmadov, I. A., and A. M. Pashajanov. "SPECTROPHOTOMETRIC RESEARCH INTO MULTI-LIGAND COMPLEXES FORMED BY ZIRCONIUM (IV) WITH STILBAZOLE AND CETYLPYRIDINIUM CHLORIDE." Chemical Problems 19, no. 4 (2021): 241–49. http://dx.doi.org/10.32737/2221-8688-2021-4-241-249.
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This study deals spectrophotometric analysis of the multi-ligand complex of zirconium (IV) with stilbazole and cetylpyridinium chloride. Dichloroethane was selected as the extragent and acetonitrile as the dispersant solution. Optimal conditions for the complex formation were identified. The results of the extraction process and complex formation were calculated statistically withPlackett Burman design and central composite design (via the Minitab 19 program). The values obtained showed that experimental results can be expressed as statistical results. Most important factors influencing absorption during complex formation were pH and ligand content. To obtain the maximum absorption, pH should be 4.5 and the ligand content should be 300 µL. The stoichiometric composition of the components in the complex was determined by various methods. The interval of subordination to Baer's law was 2-7.6 μg mL-1 , the molar light absorption coefficient was 2.6 × 104 L Mol-1 cm -1 , λmax = 590nm. A highly selective methodology was developed to determine the zirconium (IV) micronutrients in water samples.
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Gudzenko, O. V., N. V. Borzova, L. D. Varbanets, I. I. Seifullina, O. A. Chebanenko, and O. E. Martsinko. "Effect of Different Ligand and Different Ligand Heterometal Xylaratohermanates on the Activity of α-L-Rhamnosidases Eupenicillium erubescens, Cryptococcus albidus and Penicillium tardum." Mikrobiolohichnyi Zhurnal 83, no. 3 (June 17, 2021): 35–45. http://dx.doi.org/10.15407/microbiolj83.03.035.
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α-L-Rhamnosidase [EC 3.2.1.40], enzyme of the hydrolase family has a wide range of applications: in the food industry, for example, in winemaking to improve the quality and aroma of wines, in the production of citrus juices and drinks to remove bitter components (naringin) that improves the quality and nutritional value of these products; in research as an analytical tool for studying the structure of complex carbohydrate-substituted biopolymers. For the successful use of α-L-rhamnosidases in various biotechnological processes, an important aspect is the development of ways to increase their activity. The main factors affecting the growth and metabolism of microorganisms, including the synthesis of enzymes, are the physicochemical conditions of cultivation, the composition of the nutrient medium, the introduction of substances that raise the yield of the enzyme, which is manifested in an increase in its activity. At present, one of the priority directions of modern research is the study of the effect of various effector compounds that are capable to modify the studied enzymatic activity. In this work, which is a continuation of previous studies, a number of mixed-ligand and mixed-ligand-different-metal coordination germanium compounds of with xylaric acid (H5Xylar), 1,10-phenanthroline (Phen), 2,2-bipyridine (bipy) and ions of 3d-metals (Fe2+, Ni2+, Cu2+, Zn2+) were selected as effectors. Study of the effect of these complexes on the activity of Eupenicillium erubescens, Cryptococcus аlbidus and Penicillium tardum α-L-rhamnosidases were the aim of this work. Methods. The objects of research were α-Lrhamnosidases from Eupenicillium erubescens 248, Cryptococcus albidus 1001, and Penicillium tardum IMV F-100074. The α-L-rhamnosidase activity was determined by the Davis method using naringin as a substrate. We used 12 coordination compounds of germanium as modifiers of enzyme activity, the composition and structure of which were established using a combination of physical and chemical research methods: elemental analysis, thermogravimetry, IR spectroscopy and X-ray structural analysis. Structures of seven compounds are deposited in the Cambridge Crystallographic Database. When studying the effect of various compounds on the activity of enzymes, concentrations of 0.1 and 0.01% were used, exposure times were 0.5 and 24 hours. The test compounds were dissolved in 0.1% dimethyl sulfoxide. UV-spectra of absorption of native and chemical modified preparations of the enzymes were studied by spectrophotometer-fluorimeter DeNovix DS-11 in the range of 220–340 nm, concentration of the enzyme preparation 1.0 mg of protein/mL. Results. Analysis of the totality of the obtained data (exposure time 24 h, concentration 0.1%) regarding the effect of the studied compounds on the activity of E. erubescens, C. albidus and P. tardum α-L-rhamnosidases showed that the influence of the studied modifiers for the activity of α-L-rhamnosidases varies depending on the producer strain. Our data allow us to present the following series of modifiers in accordance with an increase in their effect on the activity of enzymes of different producers: E. еrubescens: 12 < 11 < 5 < 3 < 4=10 < 1 < 3 < 8 < 2 < 6 < 7; C. albidus: 10 < 11 < 12 < 9 < 3 < 1=5 < 8=4 < 2 < 6 < 7; P. tardum: 12=2 < 3 < 4 < 11 < 5 < 8 < 1 < 9 < 6 < 10 < 7. Conclusions. The results obtained allow us to conclude that compound (7)(-tris(bipyridine) nickel(II) μ-dihydroxyxylaratogermanate(IV)) is the most effective activator of α-L-rhamnosidases of all three micromycete strains, compound (6)(tris(phenanthroline)nickel(II) μ-dihydroxyxylaratogermanate(IV)) − on α-L-rhamnosidase from E. erubescens and C. albidus, while compound (10)-(copper(II) μ-dihydroxyxylaratogermanate(IV)-cuprate(II)) − only of P. tardum α-L-rhamnosidase.
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Dallaire, Frédéric, Paola Blanchette, and Philip E. Branton. "A Proteomic Approach To Identify Candidate Substrates of Human Adenovirus E4orf6-E1B55K and Other Viral Cullin-Based E3 Ubiquitin Ligases." Journal of Virology 83, no. 23 (September 16, 2009): 12172–84. http://dx.doi.org/10.1128/jvi.01169-09.
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ABSTRACT It has been known for some time that the human adenovirus serotype 5 (Ad5) E4orf6 and E1B55K proteins work in concert to degrade p53 and to regulate selective export of late viral mRNAs during productive infection. Both of these functions rely on the formation by the Ad5 E4orf6 protein of a cullin 5-based E3 ubiquitin ligase complex containing elongins B and C. E1B55K is believed to function as the substrate recognition module for the complex and, in addition to p53, Mre11 and DNA ligase IV have also been identified as substrates. To discover additional substrates we have taken a proteomic approach by using two-dimensional difference gel electrophoresis to detect cellular proteins that decrease significantly in amount in p53-null H1299 human lung carcinoma cells after expression of E1B55K and E4orf6 using adenovirus vectors. Several species were detected and identified by mass spectroscopy, and for one of these, integrin α3, we went on in a parallel study to confirm it as a bone fide substrate of the complex (F. Dallaire et al., J. Virol. 83:5329-5338, 2009). Although the system has some limitations, it may still be of some general use in identifying candidate substrates of any viral cullin-based E3 ubiquitin ligase complex, and we suggest a series of criteria for substrate validation.
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Schwartz, Rachel A., Seema S. Lakdawala, Heather D. Eshleman, Matthew R. Russell, Christian T. Carson, and Matthew D. Weitzman. "Distinct Requirements of Adenovirus E1b55K Protein for Degradation of Cellular Substrates." Journal of Virology 82, no. 18 (July 9, 2008): 9043–55. http://dx.doi.org/10.1128/jvi.00925-08.
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ABSTRACT The E1b55K and E4orf6 proteins of adenovirus type 5 (Ad5) assemble into a complex together with cellular proteins including cullin 5, elongins B and C, and Rbx1. This complex possesses E3 ubiquitin ligase activity and targets cellular proteins for proteasome-mediated degradation. The ligase activity has been suggested to be responsible for all functions of E1b55K/E4orf6, including promoting efficient viral DNA replication, preventing a cellular DNA damage response, and stimulating late viral mRNA nuclear export and late protein synthesis. The known cellular substrates for degradation by E1b55K/E4orf6 are the Mre11/Rad50/Nbs1 DNA repair complex, the tumor suppressor p53, and DNA ligase IV. Here we show that the degradation of individual targets can occur independently of other substrates. Furthermore, we identify separation-of-function mutant forms of E1b55K that can distinguish substrates for binding and degradation. Our results identify distinct regions of E1b55K that are involved in substrate recognition but also imply that there are additional requirements beyond protein association. These mutant proteins will facilitate the determination of the relevance of specific substrates to the functions of E1b55K in promoting infection and inactivating host defenses.
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Manszewski, Tomasz, Kamil Szpotkowski, and Mariusz Jaskolski. "Crystallographic and SAXS studies ofS-adenosyl-L-homocysteine hydrolase fromBradyrhizobium elkanii." IUCrJ 4, no. 3 (April 10, 2017): 271–82. http://dx.doi.org/10.1107/s2052252517002433.
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S-Adenosyl-L-homocysteine hydrolase (SAHase) from the symbiotic bacteriumBradyrhizobium elkanii(BeSAHase) was crystallized in four ligand complexes with (i) mixed adenosine (Ado) and cordycepin (Cord; 3′-deoxyadenosine), (ii) adenine (Ade), (iii) Ado and (iv) mixed 2′-deoxyadenosine (2′-dAdo) and Ade. The crystal structures were solved at resolutions of 1.84, 1.95, 1.95 and 1.54 Å, respectively. Only the Ade complex crystallized with a dimer in the asymmetric unit, while all of the other complexes formed a crystallographically independent tetrameric assembly. In the Ado/Cord complex, adenosine is found in three subunits while the fourth subunit has cordycepin bound in the active site. In the Ade and Ado complexes only these ligand molecules are present in the active sites. The 2′-dAdo/Ade complex has Ade bound in two subunits and 2′-dAdo bound in the other two subunits. The BeSAHase fold adopted a closed conformation in the complexes with Ado, Ade and 2′-dAdo, and a semi-open conformation when cordycepin occupied the active site. An SAHase-specific molecular gate, consisting of residues His342 and Phe343, behaves differently in the different complexes, but there is no simple correlation with the ligand type. Additional small-angle X-ray scattering (SAXS) experiments confirm the tetrameric state of the protein in solution. The main conclusions from this work are (i) that the SAHase subunit does not simply oscillate between two discrete conformational open/closed states in correlation with the absence/presence of a ligand in the active site, but can also assume an intermediate form for some ligands; (ii) that the shut/open state of the molecular gate in the access channel to the active site is not correlated in a simple way with the open/closed subunit conformation or empty/occupied status of the active site, but that a variety of states are possible even for the same ligand; (iii) that a cation (typically sodium) coordinated in an intersubunit loop rigidifies a molecular hinge and thus stabilizes the closed conformation; (iv) that BeSAHase in solution is a tetramer, consistent with the model derived from crystallography.
Dissertations / Theses on the topic "ADN ligase IV"
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De, Melo Abinadabe Jackson. "Molecular basis for the structural role of human DNA ligase IV." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4040.
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Les défauts dans la réparation des cassures double-brin de l'ADN (DSBs) peuvent avoir d'importantes conséquences pouvant entrainer une instabilité génomique et conduire à la mort cellulaire ou au développement de cancers. Dans la plupart des cellules mammifères, le mécanisme de Jonction des Extrémités Non Homologues (NHEJ) est le principal mécanisme de réparation des DSBs. L'ADN Ligase IV (LigIV) est une protéine unique dans sa capacité à promouvoir la NHEJ classique. Elle s'associe avec deux autres protéines structuralement similaires, XRCC4 et XLF (ou Cernunnos). LigIV interagit directement avec XRCC4 pour former un complexe stable, tandis que l'interaction entre XLF et ce complexe est médiée par XRCC4. XLF stimule fortement l'activité de ligation du complexe LigIV/XRCC4 par un mécanisme encore indéterminé. Récemment, un rôle structurel non catalytique a été attribué à LigIV (Cottarel et al., 2013). Dans le travail de thèse présenté ici, nous avons reconstitué l'étape de ligation de la NHEJ en utilisant des protéines recombinantes produites dans des bactéries afin d’une part, d'explorer les bases moléculaires du rôle structural de LigIV, d’autre part de comprendre le mécanisme par lequel XLF stimule le complexe de ligation, et enfin de mieux comprendre comment ces trois protéines coopèrent au cours de la NHEJ. Nos analyses biochimiques suggèrent que XLF via son interaction avec XRCC4 lié à LigIV, pourrait induire un changement conformationnel dans la LigIV. Ce réarrangement de la ligase exposerait son interface de liaison à l'ADN ce qui lui permettrait alors de ponter deux molécules indépendantes d'ADN, une capacité indépendante de l'activité catalytique de LigIVFailure to repair DNA double-strand breaks (DSBs) may have deleterious consequences inducing genomic instability and even cell death. In most mammalian cells, Non-Homologous End Joining (NHEJ) is a prominent DSB repair pathway. DNA ligase IV (LigIV) is unique in its ability to promote classical NHEJ. It associates with two structurally related proteins called XRCC4 and XLF (aka Cernunnos). LigIV directly interacts with XRCC4 forming a stable complex while the XLF interaction with this complex is mediated by XRCC4. XLF strongly stimulates the ligation activity of the LigIV/XRCC4 complex by an unknown mechanism. Recently, a structural noncatalytic role of LigIV has been uncovered (Cottarel et al., 2013). Here, we have reconstituted the end joining ligation step using recombinant proteins produced in bacteria to explore not only the molecular basis for the structural role of LigIV, but also to understand the mechanism by which XLF stimulates the ligation complex, and how these three proteins work together during NHEJ. Our biochemical analysis suggests that XLF, through interactions with LigIV/XRCC4 complex, could induce a conformational change in LigIV. Rearrangement of the LigIV would expose its DNA binding interface that is able to bridge two independent DNA molecules. This bridging ability is fully independent of LigIV’s catalytic activity. We have mutated this interface in order to attempt to disrupt the newly identified DNA bridging ability. In vitro analysis of this LigIV mutant will be presented as well as a preliminary in vivo analysis
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Menchon, Grégory. "Criblage virtuel et fonctionnel sur le complexe XRCC4/ADN ligase IV/Cer-XLF de ligature des cassures double-brin de l'ADN : application en radiosensibilisation tumorale." Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30395.
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En cancérologie, la radiothérapie est une des armes essentielles pour éradiquer les cellules tumorales. Les cassures des deux brins de l'ADN dites "double-brin" qu'elle induit sont particulièrement toxiques et constituent la principale cause de mort cellulaire. La NHEJ (Jonction d'Extrémités Non-Homologues) est la voie métabolique majeure de réparation de ces cassures double-brin de l'ADN et par ce mécanisme, les cellules humaines adoptent une résistance à la radiothérapie. Ce mécanisme de réparation constitue donc une cible de choix pour un traitement anticancéreux combiné en vue d'augmenter la sensibilité des cellules cancéreuses aux rayons ionisants (radiosensibilisation). Au cours du mécanisme NHEJ, la ligature finale des extrémités d'ADN est assurée par le complexe protéique tripartite: XRCC4/ADN Ligase IV/Cernunnos-XLF. Les interfaces protéiques concernées représentent toutes des cibles potentielles dans une stratégie rationnelle d'isolement de molécules inhibitrices, guidée par les structures tridimensionnelles de chaque protéine. A travers des expériences de criblage virtuel et de validation à la fois biophysique et biochimique, nous avons isolé les premières molécules capable de prévenir in vitro les interactions protéine-protéine pour les complexes XRCC4/Lig4 et XRCC4/Cer-XLF, respectivement. Ces composés sont des points de départ pour l'élaboration d'inhibiteurs potentiels de plus haute affinité grâce à l'apport de la biologie structurale, en vue d'un effet radiosensibilisant cellulaireRadiotherapy is a major weapon used against cancer. Radio-induced DNA double strand breaks (DSB) are the main lesions responsible for cell death. Non-homologous end-joining (NHEJ) is a predominant DSB repair mechanism which contributes to cancer cells resistance to radiotherapy. NHEJ is thus a good target for strategies which aim at increasing the radio-sensitivity of tumors. Through in silico screening and biophysical and biochemical assays, our objective was to find specific ligands for the XRCC4/Lig4 and XRCC4/Cer-XLF protein-protein interactions involved in NHEJ. Here, we isolated the first compounds able to prevent their interaction in vitro. These early stage inhibitors are promising tools for cancer therapy with the hope to develop more specific compounds for cellular assays through the 3D structure of the protein/inhibitor complexes
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Amram, Jérémy. "Etude structurale et fonctionnelle des complexes multi-protéiques de la voie de réparation NHEJ chez l’homme." Thesis, Paris 11, 2015. http://www.theses.fr/2015PA114822/document.
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La voie de réparation NHEJ (Non-Homologous End-Joining) est une voie majeure de réparation des cassures double-brin chez l’homme. Les protéines de cette voie interagissent et forment des complexes dynamiques dont les mécanismes moléculaires sont encore largement méconnus. Nous avons dans un premier temps mis au point des protocoles de production à l’échelle de plusieurs milligrammes des protéines cœur de la voie NHEJ en cellules d’insecte à l’aide du système MultiBac. Nous avons ainsi purifié les complexes Ku70/Ku80 et Ligase4/XRCC4 et les protéines Cernunnos et Artemis à homogénéité. Des essais de cristallisation, des études par SAXS et des analyses par microscopie électronique ont été réalisés sur différents complexes formés par ces protéines cœur du NHEJ. Nous avons également caractérisé par chromatographie d’exclusion de taille et calorimétrie, les interactions effectuées entre les protéines de la voie NHEJ. L’ensemble de ces travaux a permis d’établir des bases biochimiques solides en vue des études structurales et fonctionnelles de la voie NHEJ chez l’hommeHuman DNA repair pathway NHEJ (Non-Homologous End-Joining) is a major pathway of double-strand breaks repair. The proteins involved in this pathway interact and form dynamic complexes whose molecular mechanisms are largely unknown. Firstly, we established protocols to be able to purify milligrams of those NHEJ pathway core proteins using MultiBac insect cells system. We then purified Ku70/Ku80 and Ligase4/XRCC4 complexes, Artemis and Cernunnos to homogeneity. Crystallogenesis assays, SAXS experiments and Transmission Electronic Microscopy experiments have been performed on several complexes formed by these core NHEJ proteins. We also characterized the interactions between these proteins by Size Exclusion Chromatography and Isothermal Calorimetry. These experiments have led to biochemical results sufficient to establish a solid basis to initiate the structural and functional study of the Human NHEJ Pathway
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Lemos, Sónia Cristina Gaspar de. "Imunodeficiências primárias e neoplasias hematológicas: quando investigar?" Master's thesis, 2014. http://hdl.handle.net/10316/37429.
Full textBook chapters on the topic "ADN ligase IV"
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Chistiakov, Dimitry A. "Ligase IV Syndrome." In Advances in Experimental Medicine and Biology, 175–85. New York, NY: Springer New York, 2010. http://dx.doi.org/10.1007/978-1-4419-6448-9_16.
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Bunker, Bruce C., and William H. Casey. "Aqueous Polymerization of Silicates and Aluminosilicates." In The Aqueous Chemistry of Oxides. Oxford University Press, 2016. http://dx.doi.org/10.1093/oso/9780199384259.003.0022.
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Part Five of this book is devoted to silicates for several important reasons. First, silicates represent critical components of our planet and our lives. Silicon is the second most abundant element in Earth’s crust after oxygen, representing about 28% of the atoms present. As such, transformations of silicate minerals dominate much of the aqueous geochemistry of Earth. Every day, each of us encounters materials and objects the primary constituents of which are silicon oxides and related phases such as aluminosilicates. Granite facings on buildings, bricks, glass, pottery, ceramics, engineered materials used in water purification, catalysis, electronics, and even the optical fibers used in our most advanced communication systems are all silica based. Aluminosilicate minerals are even used as food additives. A key attribute of silicates that distinguishes them from most of the oxides highlighted in Parts One through Four of this book is that the Si(IV) cation is almost always present in a tetrahedral rather than in an octahedral coordination geometry. Exceptions include a few high-pressure phases such as stishovite (see Chapter 2) and a limited number of chelated Si(IV) complexes (see Section 14.3). The authors know of no stable compounds where Si(IV) is coordinated to only three oxygen atoms. The pathways for both forming and destroying silicate bonds are substantially different than for octahedral metal ions. Ligand-exchange pathways for silicate ions are via nucleophilic attack, where the coordination number increases in a transition state from four to five or even six (see Section 14.3 and Chapters 4 and 5). These contrast with pathways for octahedral metal ions, such as Al(III), where it is easier to decrease the coordination number from six to five or four in dissociative ligand exchange reactions. Of course, Si(IV) is not the only common element capable of forming tetrahedral oxide species. As outlined in Chapters 2 and 4, any cation with an ionic radius between roughly 0.03 nm and 0.055 nm can fit within the tetrahedral void between four close-packed oxygen anions, as expressed by Linus Pauling’s First Rule of coordination chemistry (see Chapter 2).
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Lambert, Tristan H. "Construction of Single Stereocenters." In Organic Synthesis. Oxford University Press, 2017. http://dx.doi.org/10.1093/oso/9780190646165.003.0031.
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Haifeng Du at the Chinese Academy of Sciences reported (J. Am. Chem. Soc. 2013, 135, 6810) the borane-catalyzed asymmetric hydrogenation of imine 1 to 2 using the diene 3 as a chiral ligand for boron. A single-enzyme cascade for the reductive transamination of acetophenone 4 with amine 5 to produce enantiopure sec-phenethylamine 6 was developed (Chem. Commun. 2013, 49, 161) by Per Berglund at the KTH Royal Institute of Technology in Sweden. A group at Boehringer Ingelheim in Ridgefield, Connecticut, led by Jonathan T. Reeves, disclosed (J. Am. Chem. Soc. 2013, 135, 5565) a procedure for the addition of DMF anion to N-sulfinyl imine 7 to furnish tert-leucine amide 8 with high diastereoselectivity. The tertiary carbinamine 10 was synthesized (Org. Lett. 2013, 15, 34) via the carbolithiation/rearrangement of vinylurea 9 as reported by Jonathan Clayden at the University of Manchester. Gregory C. Fu at Caltech reported (Angew. Chem. Int. Ed. 2013, 52, 2525) that the chiral phosphine 12 catalyzed the enantioselective addition of trifluoroacetamide to allene 11 to produce γ-amino ester 13 in enantioenriched form. Adeline Vallribera at the Autonomous University of Barcelona found (Org. Lett. 2013, 15, 1448) that a europium pybox complex effected the highly enantioselective α-amination of β-ketoester 14 to generate 15 on the way to the Parkinson’s disease co-drug L-carbidopa. Hisashi Yamamoto at the University of Chicago and Chubu University reported (J. Am. Chem. Soc. 2013, 135, 3411) that a halfnium(IV) complex of the bishydroxamic acid 17 catalyzed the enantioselective epoxidation of the tertiary homoallylic alcohol 16 to 18. The rearrangement of the allylic carbonate 19 to produce allyl ether 21 with high ee under iridium catalysis in the presence of ligand 20 was disclosed (Org. Lett. 2013, 15, 512) by Hyunsoo Han at the University of Texas, San Antonio. The asymmetric vinylogous aldol reaction of 3-methyl-2-cyclohexen-1-one 22 and α-keto ester 23 to furnish tertiary carbinol 25 using the bifunctional catalyst 24 was developed (Org. Lett. 2013, 15, 220) by Paolo Melchiorre at ICREA and ICIQ in Spain.
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Takaoki, Kazuo, Kotohiro Nomura, Naofumi Naga, and Akio Imai. "Synthesis of Titanium(IV) Complexes that Contain the Bis(silylamide) Ligand of the Type [1,8-C10H6(NR)2]2- (R=SiMe3, SitBuMe2, SiiPr3), and Olefin Polymerization Catalyzed by the [1,8-C10H6(NR)2] TiX2(X=Cl, Br)- cocatalyst System." In Science and Technology in Catalysis 1998, Proceedings of the Third Tokyo Conference on Advanced Catalytic Science and Technology, 469–72. Elsevier, 1999. http://dx.doi.org/10.1016/s0167-2991(99)80121-9.
Full textConference papers on the topic "ADN ligase IV"
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Akbar, Himyan, Salma Habib, Mohammed Mahroof Tahir, and Lakshmaiah Sreerama. "Synthesis and Characterization of Vanadium (IV)-Flavonoid Complexes and its Antioxidant ability toward Superoxide and Radical Scavenging." In Qatar University Annual Research Forum & Exhibition. Qatar University Press, 2020. http://dx.doi.org/10.29117/quarfe.2020.0109.
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In this project Vanadium complex -Vanadium (IV) - flavone was synthesized using vanadium (IV) acetylacetonate (VO(acac)2) complex and 3-hydroxy-6-methyl flavone ligand. The complex stability was checked using FTIR and UV-vis spectroscopies. Peackes around 990 cm-1 conforms the formation of (V=O) in the complex, as well as (V-O) around 790 cm-1. In UV-Vis spectrum peak around 400-450 nm was noticed, which conforms the formation of the vanadium complex that correspond to the ligand to metal charge transfer (LMCT) transition. The radical scavenging abilities of vanadium complex were investigated using DPPH. The anti-oxidant activity using (BHA) as a standard reference, the complex synthesized displayed strong DPPH antioxidant radical scavenging activity compared to VO(acac)2 and BHA, with IC50 value of (105, 95 and 96) mM respectively. The absorbance in which the reducing power occurred were found to be (0.397, 0.825 and 0.228) for the complex, VO(acac)2 and BHA.
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"Synthesis, Characterization and Antibacterial Activity of Organotin (IV) Complexes with Benzoylacetone Benzhydrazone Ligand." In 3rd International Conference on Biological, Chemical and Environmental Sciences. International Institute of Chemical, Biological & Environmental Engineering, 2015. http://dx.doi.org/10.15242/iicbe.c0915063.
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Lin, Tingting, Zhilian Zhou, Lifeng Zhu, Yandan Fan, Xiaofen Ding, and Yingming Sun. "Abstract 3066: DNA ligase IV inhibitor and X-ray exert a synthetic lethal in loss-of-function p53 cells." In Proceedings: AACR Annual Meeting 2021; April 10-15, 2021 and May 17-21, 2021; Philadelphia, PA. American Association for Cancer Research, 2021. http://dx.doi.org/10.1158/1538-7445.am2021-3066.
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Wei, Meng, Qian’ge He, Xuegang Liu, and Jing Chen. "N,N,N′,N′-Tetra-Methyl-3-Oxy-Pentane-1,5-Diamide (TMPDA): A Promising Back Extractant for Ln(III) and Zr(IV)." In 18th International Conference on Nuclear Engineering. ASMEDC, 2010. http://dx.doi.org/10.1115/icone18-29358.
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Water-soluble oxa-diamide ligand, N,N,N′,N′-tetra-methyl-3-oxy-pentane-1,5-diamid (TMPDA) has been synthesized and purified. Its crystal structure, melting point, decomposition temperature, solubilities in aqueous phase and organic phase, distribution ratio between aqueous and organic phase, etc. are reported. The effect of TMPDA concentration in aqueous phase and HNO3 concentration in the equilibrium aqueous phase on the extraction efficiency of La(III), Ce(III), Pr(III), Nd(III), Zr(IV), Fe(III), Y(III), Mo(VI), Ru(III) and Pd(II) by 30% TRPO/kerosene have been studied. The results indicate that TMPDA dissolve well in aqueous phase but almost insoluble in kerosene or 30%TRPO/kerosene in the bi-phase system. It can effectively reduce the extraction of Ln(III), Y(III) and Zr(IV) into 30%TRPO/kerosene at a moderate acid system (0.24mol/L∼0.27mol/L HNO3). TMPDA is a promising stripping agent for Ln(III), Y(III) and Zr(IV) from loaded TRPO.
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Šeklić, Dragana, Milena Jovanović, Nevena Milivojević, and Marko Živanović. "PLATINUM(IV) COMPLEX AND ITS CORRESPONDING LIGAND SUPPRESS CELL MOTILITY AND PROMOTE EXPRESSION OF FRIZZLED-7 RECEPTOR IN COLORECTAL CANCER CELLS." In 1st INTERNATIONAL Conference on Chemo and BioInformatics. Institute for Information Technologies, University of Kragujevac, 2021. http://dx.doi.org/10.46793/iccbi21.288s.
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Suppression of cell movement is an imperative in the effectiveness of future generations of chemotherapeutics. Frizzled 7 receptor (FZD7), as the first protein of Wnt/β-catenin signaling cascade, plays a significant role in regulation of cell differentiation, proliferation, and cell migration. This study aimed to investigate the potential effects of platinum (IV) complex: [PtCl4 (dbu-S, S-eddp)] – C1, and its corresponding ligand – L1 on cell movement, as well as the FZD7 expression and localization after treatments on two human colorectal carcinoma cell lines (HCT-116, SW-480). A Wound healing assay was used to examine cell migration, while FZD7 protein expression was examined by immunofluorescence. Chemical compounds, especially L1, reduced cell motility of both tested cell lines. They showed a particularly good effect on HCT-116 cells, increasing protein expression of the antimigratory marker FZD7 whose localization was observed on the cell membrane of HCT-116 cells. Suppression of cell movement was significantly lower in SW-480 cells after treatments, when compared to HCT-116, with an obvious decrease of FZD7 receptor expression and its localization in the cytoplasm of these cells. Our results indicate that among the examined treatments, the ligand showed more significant results in the suppression of HCT-116 cell movement, most likely through the stimulation of differentiation, which is indicated by the promotion of FZD7 expression.
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Narendran, N. K. Siji, Rahul Soman, P. Sudheesh, Chellaiah Arunkumar, and K. Chandrasekharan. "χ(3) measurements of axial ligand modified high valent tin(IV) porphyrins using degenarete four wave mixing at 532nm." In LIGHT AND ITS INTERACTIONS WITH MATTER. AIP Publishing LLC, 2014. http://dx.doi.org/10.1063/1.4898288.
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Zeeshan, Mahira, and Hussain Ali. "Design of ligand anchored polymeric nanoparticles for potential targeted drug delivery in intestinal inflammation." In IV. Symposium of Young Researchers on Pharmaceutical Technology,Biotechnology and Regulatory Science. Szeged: Institute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Faculty of Pharmacy, 2022. http://dx.doi.org/10.14232/syrptbrs.2022.27.
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Johari, Surabhi, Rajeev Sharmah, and Subrata Sinha. "Ligand binding studies for DPP IV a target protein responsible for Diabetes Mellitus Type 2: Structural based approach for drug designing." In 2011 2nd National Conference on Emerging Trends and Applications in Computer Science (NCETACS). IEEE, 2011. http://dx.doi.org/10.1109/ncetacs.2011.5751401.
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Modesti, P. A., A. Fortini, M. Boddi, L. Poggesi, R. Abbate, and G. F. Gensini. "REVERSIBLE REDUCTION OF PLATELET PROSTACYCLIN BINDING SITES AFTER ILOPROST INFUSION IN MAN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643454.
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The reduction of platelet sensitivity to prostacyclin (PGI2), observed in man after the infusion of PGI2 analogues, could suggest the presence of a down regulation mechanism for PGI2 platelet receptors. Robertson (1980) have shown a dcwn-regulaticn of PGE2 binding after PGE2 infusion in rat and Leigfrt (1985) have provided evidence of an homologous desensitizaticn to PGI2 in cultured cells, but direct evidences of PGI2 receptors dcwn-regulaticn in man are lacking.This work was performed to study the behaviour of PGI2 platelet receptors after a PGE2 analogue infusion in man.Eight subjects with peripheral artery disease (stage IV according to Fontaine) treated for 14 consecutive days with six hours iv infusion of Iloprost (Sobering, FRG) at 2 ng/Kg/min were studied. Platelet studies were performed an the 1st, 2nd, 7th and 14th day of therapy, blood sanples being collected immediately before the beginning (between 8.00 and 9.00 a.m.), at the end and 6 and 18 hours (the following morning) after the end of the infusion. PGI2 platelet receptors were investigated by a direct radioligand binding assay. PGI2 inhibitory dose 50 (I.D.50) was evaluated in platelet aggregation induced by ADP 5 ¼M.After six hours of Iloprost infusion a significant reduction of high affinity PGI2 platelet receptor (HAR) nunber was observed (p<0.005) without any change of affinity for the ligand. After 6 hours from the end of the infusion the reduction of the HAR was still statistically significant (p<0.05). The following morning the receptor nunber was restored (n.s.). After one and two weeks from the beginning of the treatment the basal values of PGI2 HAR were not significantly changed from the values recorded on the first day of therapy.PGI2 I.D.50 after the infusion was significantly increased when compared to the basal values (p<0.01). Six hours later the basal sensitivity was restored (n.s.). Eighteen hours later, the following morning PGI2 I.D.50 were still not significantly changed in comparison to the basal values.These data are suggestive for the presence of a reversible down regulation mechanism for the PGI2 receptors.
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SOARES, Roniere Leite, Walman Benício de CASTRO, José Lion Oliveira JULIÃO, and Kleanny Gama Sales de SOUZA. "Potencial da ferramenta computacional OriginPro 8 SRO v8.0724 (B724) na geração de funções não-lineares que descrevem curvas exotérmica e endotérmica numa liga metálica Ni50Ti30Hf20 .at% com EMF." In IV World Congress on Systems Engineering and Information Technology. Recife, Brasil: Even3, 2017. http://dx.doi.org/10.29327/111252.4-1.
Full textReports on the topic "ADN ligase IV"
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Szigethy, Geza. Rational Ligand Design for U(VI) and Pu(IV). Office of Scientific and Technical Information (OSTI), August 2009. http://dx.doi.org/10.2172/972716.
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Altstein, Miriam, and Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, August 2013. http://dx.doi.org/10.32747/2013.7593398.bard.
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The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.
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Altstein, Miriam, and Ronald Nachman. Rationally designed insect neuropeptide agonists and antagonists: application for the characterization of the pyrokinin/Pban mechanisms of action in insects. United States Department of Agriculture, October 2006. http://dx.doi.org/10.32747/2006.7587235.bard.
Full textAbstract:
The general objective of this BARD project focused on rationally designed insect neuropeptide (NP) agonists and antagonists, their application for the characterization of the mechanisms of action of the pyrokinin/PBAN (PK-PBAN) family and the development of biostable, bioavailable versions that can provide the basis for development of novel, environmentally-friendly pest insect control agents. The specific objectives of the study, as originally proposed, were to: (i) Test stimulatory potencies of rationally designed backbone cyclic (BBC) peptides on pheromonotropic, melanotropic, myotropic and pupariation activities; (ii) Test the inhibitory potencies of the BBC compounds on the above activities evoked either by synthetic peptides (PBAN, LPK, myotropin and pheromonotropin) or by the natural endogenous mechanism; (iii) Determine the bioavailability of the most potent BBC compounds that will be found in (ii); (iv) Design, synthesize and examine novel PK/PBAN analogs with enhanced bioavailability and receptor binding; (v) Design and synthesize ‘magic bullet’ analogs and examine their ability to selectively kill cells expressing the PK/PBAN receptor. To achieve these goals the agonistic and antagonistic activities/properties of rationally designed linear and BBC neuropeptide (NP) were thoroughly studied and the information obtained was further used for the design and synthesis of improved compounds toward the design of an insecticide prototype. The study revealed important information on the structure activity relationship (SAR) of agonistic/antagonistic peptides, including definitive identification of the orientation of the Pro residue as trans for agonist activity in 4 PK/PBANbioassays (pheromonotropic, pupariation, melanotropic, & hindgut contractile) and a PK-related CAP₂b bioassay (diuretic); indications that led to the identification of a novel scaffold to develop biostbiostable, bioavailable peptidomimetic PK/PBANagonists/antagonists. The work led to the development of an arsenal of PK/PBAN antagonists with a variety of selectivity profiles; whether between different PKbioassays, or within the same bioassay between different natural elicitors. Examples include selective and non-selective BBC and novel amphiphilic PK pheromonotropic and melanotropic antagonists some of which are capable of penetrating the moth cuticle in efficacious quantities. One of the latter analog group demonstrated unprecedented versatility in its ability to antagonize a broad spectrum of pheromonotropic elicitors. A novel, transPro mimetic motif was proposed & used to develop a strong, selective PK agonist of the melanotropic bioassay in moths. The first antagonist (pure) of PK-related CAP₂b diuresis in flies was developed using a cisPro mimetic motif; an indication that while a transPro orientation is associated with receptor agonism, a cisPro orientation is linked with an antagonist interaction. A novel, biostablePK analog, incorporating β-amino acids at key peptidase-susceptible sites, exhibited in vivo pheromonotropic activity that by far exceeded that of PBAN when applied topically. Direct analysis of neural tissue by state-of-the-art MALDI-TOF/TOF mass spectrometry was used to identify specific PK/PK-related peptides native to eight arthropod pest species [house (M. domestica), stable (S. calcitrans), horn (H. irritans) & flesh (N. bullata) flies; Southern cattle fever tick (B. microplus), European tick (I. ricinus), yellow fever mosquito (A. aegypti), & Southern Green Stink Bug (N. viridula)]; including the unprecedented identification of mass-identical Leu/Ile residues and the first identification of NPs from a tick or the CNS of Hemiptera. Evidence was obtained for the selection of Neb-PK-2 as the primary pupariation factor of the flesh fly (N. bullata) among native PK/PK-related candidates. The peptidomic techniques were also used to map the location of PK/PK-related NP in the nervous system of the model fly D. melanogaster. Knowledge of specific PK sequences can aid in the future design of species specific (or non-specific) NP agonists/antagonists. In addition, the study led to the first cloning of a PK/PBAN receptor from insect larvae (S. littoralis), providing the basis for SAR analysis for the future design of 2ⁿᵈgeneration selective and/or nonselective agonists/antagonists. Development of a microplate ligand binding assay using the PK/PBAN pheromone gland receptor was also carried out. The assay will enable screening, including high throughput, of various libraries (chemical, molecular & natural product) for the discovery of receptor specific agonists/antagonists. In summary, the body of work achieves several key milestones and brings us significantly closer to the development of novel, environmentally friendly pest insect management agents based on insect PK/PBANNPs capable of disrupting critical NP-regulated functions.